Epidemiological and clinical characteristics of hospitalized human metapneumovirus patients in Israel, 2015-2021: A retrospective cohort study.

This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015-2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single-center, retrospective cohort study was performed, including pediatric and adult patients with laboratory-confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0-2, 3-17, 18-59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults.

Gravitational Dose-Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm.

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose-response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head-up tilt to 45° head-down tilt in 15° increments, in both supine and prone postures. We measured the steady-state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose-response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head-down tilt positions.

Reducing Metabolic Cost During Planetary Ambulation Using Robotic Actuation.

INTRODUCTION: Current spacesuits are cumbersome and metabolically expensive. The use of robotic actuators could improve extravehicular activity performance. We propose a novel method to quantify the benefit of robotic actuators during planetary ambulation.METHODS: Using the OpenSim framework, we completed a biomechanical analysis of three walking conditions: unsuited, suited with the extravehicular mobility unit (EMU) spacesuit (represented as external joint torques applied to human joints), and suited with the EMU and assisted by robotic actuators capable of producing up to 10 Nm of torque. For each scenario, we calculated the inverse kinematics and inverse dynamics of the lower body joints (hip, knee, and ankle). We also determined the activation of muscles and robotic actuators (when present). Finally, from inverse dynamics and muscle activation results, the metabolic cost of one gait cycle was calculated in all three conditions.RESULTS: The moments of lower body joints increased due to the increased resistance to movement from the spacesuit. The additional torque increased the overall metabolic cost by 85 compared to the unsuited condition. The assistive robotic actuators were able to reduce the metabolic cost induced by EMU resistance by 15.DISCUSSION: Our model indicates that the majority of metabolic cost reduction can be attributed to the actuators located at the hip. The robotic actuators reduced metabolic cost similar to that of modern-day actuators used to improve walking. During a Mars mission, the actuators could save one crewmember up to 100,000 kilocal on one 539-d planetary expedition.Kluis L, Keller N, Bai H, Iyengar N, Shepherd R, Diaz-Artiles A. Reducing metabolic cost during planetary ambulation using robotic actuation. Aerosp Med Hum Perform. 2021; 92(7):570578.

Adenovirus load correlates with respiratory disease severity among hospitalized pediatric patients.

OBJECTIVES: Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal and other infections. We investigated the correlation between adenovirus viral load in clinical respiratory samples and the respiratory disease severity in pediatric patients. METHODS: Medical records of patients hospitalized in the Sheba Medical Center (SMC) with confirmed adenovirus infection were retrospectively analyzed. The possible correlation between disease severity score and Real time PCR 'cycle threshold' (Ct), a proxy of viral load, was assessed in patients aged 9 years and under. In addition, Ct values of hospitalized versus community-care patient samples, positive for various respiratory viruses including adenovirus, were compared. RESULTS: Adenovirus load in respiratory samples, as measured by Ct values, was found to be negatively correlated with respiratory disease severity in hospitalized pediatric patients aged under 9 years. Moreover, hospitalized patients presented with significantly higher Ct levels for various respiratory viruses as compared to community-care patients. CONCLUSION: In this study we found a correlation between Ct values obtained from adenovirus q-PCR analysis of respiratory clinical samples and disease severity in patients aged 9 years and under. Such finding may serve as a predictor of respiratory disease course in pediatric patients and will be beneficial for the differential diagnosis and treatment of pediatric patients.

Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients.

BACKGROUND: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. METHODS: Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database. Data including demographics, clinical course, and outcome were collected. Pharmacokinetic samples were obtained from two younger patients to guide dosing. RESULTS: In total, three patients (4.5, 5, and 19 years of age) with invasive mucormycosis who were treated with isavuconazole were identified. All patients were treated with isavuconazole as a second line therapy and experienced improvement following the initiation of this treatment. CONCLUSIONS: Based on our limited clinical experience, isavuconazole may be a safe and effective treatment option for children and adolescents afflicted by IMI. Prospective clinical trials should be performed in order to evaluate the pharmakokinetics and safety of isavuconazole in the pediatric population.

Management of sexually transmissible infections in the era of multiplexed molecular diagnostics: a primary care survey.

Background Data regarding sexually transmissible infections (STI) often originate from STI clinics, screening programs or laboratory-based studies, thus are biased for specific risk groups or lack clinical details. This real-life observational study presents sample data of most young adult Israeli population by exploiting the centralised diagnostic and documentation platforms resulting from a mandatory military service at the age of 18 years for both genders. METHODS: All STI diagnoses of Israeli Defence Forces soldiers during a 6-month period were reviewed. Patients with Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) (major-STI) and Ureaplasma urealyticum (UU), Ureaplasma parvum (UP) and Mycoplasma hominis (MH) (equivocal STI) were compared with STI-negative controls. RESULTS: Sexually transmissible infection positivity rates (n=2816) were as follows: CT 6.6%; MG 1.9%; NG 0.7%; TV 0.5%; UU 15.7%; UP 28.2%; and MH 6.2%. The CT+MG coinfection rate was 4.1%, yet CT+NG coinfections were rare (≈0.5%). More than half of the patients with ureaplasmas and/or MH were treated; 40% of them were recommended partner treatment. Most antibiotics were prescribed to patients with equivocal infections. Classic STI symptoms in males were linked to major-STI and UU, while females were asymptomatic or presented non-specific symptoms. CONCLUSIONS: The judicious use of antibiotics in the era of antimicrobial resistance necessitates re-evaluating the significance of equivocal pathogen detection and reporting (MH, UU, UP). Likewise, universal empiric treatment for NG should be reconsidered in light of its low rates in non-high-risk groups. Conversely, a high MG rate, a pathogen with potential resistance to common STI protocols, requires evaluation of guidelines adequacy.

Mutation in West Nile Virus Structural Protein prM during Human Infection.

A mutation leading to substitution of a key amino acid in the prM protein of West Nile virus (WNV) occurred during persistent infection of an immunocompetent patient. WNV RNA persisted in the patient's urine and serum in the presence of low-level neutralizing antibodies. This case demonstrates active replication of WNV during persistent infection.

Coxiella burnetii Endocarditis and Aortic Vascular Graft Infection: An Underrecognized Disease.

BACKGROUND: Q fever is considered endemic worldwide, and endocarditis, or aortic vascular infection, or both caused by Coxiella burnetii can be a fatal disease. The importance of surgical intervention has not yet been defined. We performed a descriptive retrospective study to assess indications for surgical treatment, timing of treatment, and outcome. METHODS: We studied all patients from the cardiac surgery department of a large tertiary hospital who underwent valve surgical procedure due to endocarditis or aortic surgical procedure due to graft infection. RESULTS: Throughout a 10-year period, we performed a total of 171 procedures due to valve endocarditis and/or vascular infection. In 16 patients (9.36%) Coxiella burnetii infection was diagnosed. Ten patients had previous cardiac surgical procedures, 3 had previous aortic surgical procedures, 2 had preexisting valvular disease, and 1 patient had no previous valve disorder. All patients received prolonged oral-specific antibiotic therapy under serologic guidance. In 9 patients antibiotic treatment (doxycycline and hydroxychloroquine) was started before the surgical procedure (12.4 ± 37.5 days), and in 7 patients after the surgical procedure (5.1 ± 13.5 days). We observed one in-hospital death (6.25%) and no long-term mortality. The mean follow-up period was 50.5 ± 34.7 months (range, 2 to 104 months). CONCLUSIONS: In this series surgical treatment yielded good results for both Q fever endocarditis and vascular graft infection. No association was found between timing of the surgical procedure and patients' outcomes.

Colonic carriage of Streptococcus bovis and colorectal neoplasia: a prospective 17-year longitudinal case-control study.

BACKGROUND: Patients with Streptococcus bovis infective endocarditis have an increased prevalence of advanced colonic neoplasia; however, an association with fecal carriage of the organism is unclear. S. bovis has been shown to promote colonic neoplasia in preclinical studies. The aim of this study was to examine the effect of S. bovis fecal carriage on the long-term risk of colonic neoplasia. PATIENTS AND METHODS: Patients were prospectively recruited before colonoscopy. S. bovis was detected by culture in stool, colonic fluid aspirates, and biopsies. Patients continued colonoscopic surveillance at intervals according to accepted guidelines. The National Cancer Registry was checked for diagnoses of colorectal cancer on 31 December 2014. RESULTS: A total of 118 patients were recruited [75 (72.8%) men, aged 64.5±9.3 years] including 15 with S. bovis. The mean duration of follow-up was 190.7±123.5 months. Colonic neoplasia was detected at colonoscopy in six (40.0%) and 49 (47%) patients with and without S. bovis, respectively (P=0.78). At the end of follow-up, colorectal cancer had developed in one (6.7%) S. bovis-positive and six (5.8%) S. bovis-negative patients (P=1.00). CONCLUSION: Fecal carriage of S. bovis at baseline is not associated with an increased long-term risk of developing colonic neoplasia in this longitudinal study.

Nocardia Colonization: A Risk Factor for Lung Deterioration in Cystic Fibrosis Patients?

BACKGROUND: Cystic fibrosis (CF) patients are predisposed to infection and colonization with different microbes. Some cause deterioration of lung functions, while others are colonizers without clear pathogenic effects. Our aim was to understand the effects of Nocardia species in sputum cultures on the course of lung disease in CF patients. MATERIAL AND METHODS: A retrospective study analyzing the impact of positive Nocardia spp. in sputum of 19 CF patients over a period of 10 years, comparing them with similar status patients without Nocardia growth. Pulmonary function tests (PFTs) are used as indicators of lung disease severity and decline rate in functions per year is calculated. RESULTS: No significant difference in PFTs of CF patients with positive Nocardia in sputum was found in different sub-groups according to number of episodes of growth, background variables, or treatment plans. The yearly decline in PFTs was similar to that recognized in CF patients. The control group patients showed similar background data. However, a small difference was found in the rate of decline of their PFTs, which implies a possibly slower rate of progression of lung disease. CONCLUSIONS: The prognosis of lung disease in CF patients colonized with Nocardia does not seem to differ based on the persistence of growth on cultures, different treatment plans or risk factors. Apparently, Nocardia does not cause a deterioration of lung functions with time. However, it may show a trend to faster decline in PFTs compared to similar status CF patients without isolation of this microorganism in their sputum.

Leiomyosarcoma of the Vagina: An Exceedingly Rare Diagnosis.

Background. Primary leiomyosarcoma of the vagina is an exceedingly rare diagnosis. Current estimates are that this tumor could at most represent a mere 0.062% of malignant neoplasms in the female genital tract, although in actuality it is likely far less common. Case Presentation. A 70-year-old female gravida 3 para 2 with new onset palpable vaginal mass and pink vaginal discharge is diagnosed with primary leiomyosarcoma of the vagina. Chemotherapy is complicated by acute Lyme disease, and the patient requires a robotic-assisted total hysterectomy with bilateral salpingo-oophorectomy and partial vaginectomy. The patient remains without recurrence 18 months after surgery. Conclusion. Vaginal leiomyosarcoma is exceedingly rare with an aggressive course, high recurrence, and undetermined ideal treatment regimen. Its diagnosis can be delayed and its presentation varied. Information on this rare tumor type is predominantly through rare case reports with collective consensus on management lacking. The gynecologic oncologist must exercise prudence in individualizing treatment regimens for this rare yet aggressive malignancy.

Do immunocompromised children benefit from having surgical lung biopsy performed?

BACKGROUND: Surgical lung biopsy is considered a gold standard for the evaluation of pulmonary disease in immunocompromised children. However, in the literature, its accuracy and the rate of complications vary. OBJECTIVE: We aimed to evaluate the yield of surgical lung biopsies in the management of persistent pulmonary findings in immunocompromised children. METHODS: We performed a retrospective review of clinical records of immunocompromised children who underwent surgical lung biopsies, and evaluated the impact that preoperative factors had on outcomes. RESULTS: Twenty-five patients underwent 27 surgical lung biopsies. The underlying immunodeficiency included allogeneic stem cell transplantation (n = 12), chemotherapy for solid tumors (n = 6), hematologic malignancy (n = 4), primary immunodeficiency (n = 4) and chronic steroid use (n = 1). Biopsies provided a specific histopathologic or microbiologic diagnosis in 10 cases (37%). No preoperative factor predicted a diagnostic biopsy. Five of the 27 biopsies were beneficial for the patients (18%). A major complication related to the procedure was reported for 1 biopsy (4%). CONCLUSIONS: We conclude that surgical lung biopsy in pediatric immunocompromised patients appears to be safe, but has a relatively low diagnostic yield and an even lower yield with regards to the benefit it provides.

High rate of human bocavirus and adenovirus coinfection in hospitalized Israeli children.

We investigated coinfection of human bocavirus (HBoV) and other respiratory viruses in hospitalized children by real-time PCR. A high rate (69.2%) of adenovirus infection was found among children infected with HBoV. Such high rates of HboV-adenovirus coinfection have not been previously reported, underscoring the need to investigate the contribution of HBoV in patient clinical presentations.

Nosocomial bloodstream infections in a pediatric intensive care unit: 3-year survey.

BACKGROUND: Bloodstream infections (BSI) represent a major cause of hospital-acquired infections in pediatric intensive care unit (PICU) patients. This study was designed to determine the prevalence, risk factors and outcomes of these infections in one local facility. MATERIAL/METHODS: All patients admitted to one PICU between January 1, 2000 - December 31, 2002 and subsequently developed a nosocomial bloodstream infection (NBSI) were consecutively recruited. The study was a retrospective study. Data retrieved from medical records included demographic information, extrinsic (invasive devices) and intrinsic risk factors, specific pathogens, therapeutic interventions and outcome. RESULTS: There were 95 episodes of NBSIs in 59 patients (63/1711 PICU admissions, yielding an incidence of 56/1000). The crude mortality rate (CMR) in children with NBSIs was 52%, compared with 6% for all other children admitted to the PICU. A higher CMR was associated with hemato-oncology illness, prolonged length of hospitalization (>1 month) mechanical ventilation, dialysis and severity of illness. Most of the patients (95%) had central intravascular devices, and 73% of the episodes were catheter-related infections. The most frequent pathogens were coagulase-negative staphylococci (24%), Klebsiella pneumonia (16%), Candida spp. (15%), Pseudomonas aeruginosa (7%) and Staphylococcus aureus (6%). Thirty-three percent of the Staphylococcus aureus were methicillin resistant (MRSA) and 30% of the Klebsiella pneumonia were extended - spectrum beta-lactamase - producing (ESBL) strains. CONCLUSIONS: The overall incidence of NBSIs was 56 episodes per 1000 admissions. The major risk factors were hemato-oncology illness, prolonged length of hospitalization, mechanical ventilation, dialysis and severity of illness. Children with NBSI had a poor outcome when compared with children without NBSI.

MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokines. MCP-1 has been previously shown to have a major role in the migration of monocytes towards human leukemic cells, yet it cannot increase cytotoxic effects of monocytes on human leukemic cells. AIM: To determine levels of MCP-1 in the CSF of children during various stages of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A 19 children with ALL and without known CNS involvement were enrolled in the study. CSF samples were aliquoted at different stages of therapy (diagnosis, induction, and maintenance) and were frozen at -70 degrees C until use. MCP-1 was measured with a sandwich enzyme-linked immunoabsorbent assay. RESULTS: Mean MCP-1 levels in the CSF were 1762.38 pg/ml (range 522-5000 pg/ml). In children without CNS involvement at diagnosis, CSF MCP1 levels did not change over time and remained within this range throughout the diagnosis and treatment stages. CNS involvement was associated with an increased MCP-1 level following chemotherapy, in patients with CNS involvement from 840 to 3990 pg/ml (P<0.0001), and in patients without CNS involvement from 1134 to 1943 pg/ml (P-value of 0.0322). White blood cells found in the CSF at diagnosis have vanished after induction. CONCLUSIONS: CNS involvement in ALL is associated with significantly higher levels of MCP1 during therapy. This significant rise in MCP-1 levels might be one of the mechanisms involved in the regulation of CNS leukemia. Since chemokines target specific leukocyte subsets, inhibition of a single Chemokine ligand or receptor may have a circumscribed effect, endowing the inhibitor with a limited side effect profile. Chemokines should be considered as possible targets for therapeutic intervention.

Seasonal variations in rhino-cerebral Mucor infection.

OBJECTIVES: Rhino-orbito-cerebral mucormycosis (ROCM) is an uncommon, potentially lethal infection that occurs mostly in immunocompromised hosts. The seasonal occurrence of ROCM was studied in two of Israel's largest medical centers. METHODS: A total of 36 patients were seen during a 25-year period in this retrospective bi-institutional cohort study. Meteorologic data were obtained and analyzed for a possible linkage of infection with precipitation and temperature. RESULTS: Twenty-one of the 36 patients (58%) presented between the months of August and October, and 27 patients (75%) presented between the months of August and December. A peak incidence of ROCM was noted in the month of September (13/36 patients; 36%). No association was noted between meteorologic conditions and the incidence of ROCM infection. CONCLUSIONS: A consistent seasonal peak was observed in ROCM. Heightened awareness is important for early recognition and treatment of this disease.

Clinical and epidemiological aspects of infections caused by fusarium species: a collaborative study from Israel.

Fusarium infections are an important problem worldwide, commonly affecting immunocompromised individuals. We conducted a retrospective study in two Israeli tertiary medical centers of factors predisposing to infection by Fusarium spp. and their influence on the epidemiology and clinical outcome of this infection. Fusarium spp. were isolated from 89 patients with a median age of 57 years. Sixty-eight patients were considered immunocompetent. Seven patients had disseminated disease, 34 had locally invasive disease, and 48 had superficial infection. Most infections were limited and occurred mainly in lower limbs. Factors associated with in-hospital mortality were chronic renal failure, hematological malignancy, immunosuppression, disseminated infection, and positive blood culture. Multivariate analysis showed that chronic renal failure, hematological malignancy, burns, and disseminated infection were independently associated with mortality. A surge in the frequency of infections was noticed during the summer for patients from rural areas, involving mainly the eyes and lungs. At one of the hospitals (in a mountainous area), there was an increase in the isolation rate over time.

Rhino-orbital and rhino-orbito-cerebral mucormycosis.

BACKGROUND: Rhino-orbito-cerebral mucormycosis (ROCM) is a devastating infection of immunocompromised hosts. We present our experience with 19 ROCM cases and attempt to define preferred diagnostic and treatment protocols. METHODS: All had tissue biopsies obtained studied by direct smear, histologic studies, and cultures. Imaging was obtained in 14 cases. RESULTS: Sixteen patients presented between August and November. Six had mixed fungal infections. Seven patients had end-stage underlying disease or infection and did not undergo surgery and 4 had an indolent form of disease. Patients were treated by surgery and by amphotericin B. The overall survival was 47%. CONCLUSIONS: ROCM may have seasonal incidence peaking in the fall and early winter. The therapeutic approach should be unchanged in cases of mixed fungal infections. Amphotericin B with aggressive debridement remains the mainstay of treatment. Early recognition and treatment are essential. A presentation and survival-dependent classification of ROCM are offered.

Listeria monocytogenes infection in Israel and review of cases worldwide.

Listeria monocytogenes, an uncommon foodborne pathogen, is increasingly recognized as a cause of life-threatening disease. A marked increase in reported cases of listeriosis during 1998 motivated a retrospective nationwide survey of the infection in Israel. From 1995 to 1999, 161 cases were identified; 70 (43%) were perinatal infections, with a fetal mortality rate of 45%. Most (74%) of the 91 nonperinatal infections involved immunocompromised patients with malignancies, chronic liver disease, chronic renal failure, or diabetes mellitus. The common clinical syndromes in these patients were primary bacteremia (47%) and meningitis (28%). The crude case-fatality rate in this group was 38%, with a higher death rate in immunocompromised patients.